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Tuesday, February 5, 2013

Generic Drugs: Bioequivalent and Interchangeable?

Use of generic drugs has the potential to reduce annual consumer spending on prescriptions by billions. A study published in the New England
Journal of Medicine and discussed in the New
York Times Economix blog in 2012 looked at Medicare Part D expenditures and
correlated them with drug prescribing patterns. The regions of the United
States with the highest Medicare expenditures were those where more name brand
drugs were prescribed. But, are generic drugs as safe and effective as name brand drugs?

Generic medications become available after brand name drugs
go off patent (usually 10 to 14 years after coming to market). The
pharmaceutical industry maintains that the high cost of brand name drugs
relates to the research and development required to innovate and bring new
products to market.Advertising and
promotion are also, no doubt, a major factor.

A generic drug is a drug that has been determined to be the bioequivalent
of a brand name drug in terms of its active ingredient.Standards for proving bioequivalence are
defined by the FDA and are similar to standards used in Canada, Japan and
Europe.Here’s what the FDA
website says about bioequivalence:

“One way scientists demonstrate bioequivalence is to measure
the time it takes the generic drug to reach the bloodstream and its concentration
in the bloodstream in 24 to 36 healthy, normal volunteers. This gives them the
rate and extent of absorption-or bioavailability-of the generic drug, which
they then compare to that of the pioneer drug. The generic version must deliver
the same amount of active ingredients into a patient's bloodstream in the same
amount of time as the pioneer drug.”

The following graph illustrates
the bioavailability of two drugs, Drug A and Drug B. The statistics may be
difficult to understand, but to be determined bioequivalent the 90% confidence interval of the ratios of the mean
bioavailability, or “area under the curve” (AUC), of the two drugs and their
peak concentrations (Cmax) must be in the ranges of 80 to 125%.In more concrete terms, analyses of numerous
studies of bioequivalence have shown that differences in blood concentrations
of the active ingredients of branded versus generic drugs are generally less
than 4 percent.

Once a generic drug is deemed to be bioequivalent by these statistical
standards it is not required to go through the same extensive clinical
safety and efficacy trials, as a newly innovated brand name drug applying for its
initial patent.

What are some pitfalls of using generics? The inactive
ingredients in generics compared with branded drugs are not required to be the
same. Therefore allergies to these fillers and inactive compounds can be an
issue. Also, special consideration should be taken when changing from a branded
drug to a generic drug, or when changing between generics, if the drug has a narrow therapeutic index. Some drugs
with narrow therapeutic indices include thyroid medications, anti-epileptics
and warfarin.

Here are some examples of issues that come up with generics:

The adhesive contained in a fentanyl transdermal patch
differs depending on whether the patch is generic or brand name. Some of my
patients have developed allergies to the adhesive in the brand name patch (as
opposed to the generic,) others complain that the generics don’t stick as well.

Along the lines of narrow therapeutic index—I can recall two
separate instances in which a patient was changed to a new warfarin generic drug
product. In each case the patient’s PT and INR (coagulation test) had been
stable for months, but after the change their levels of anti-coagulation became
too high. This took some detailed history-taking to figure out. One review of the literature
suggested that generic warfarin and Coumadin products are equally effective and
safe and uphold the FDA’s criteria for bioequivalence, yet the authors still
suggested that patients limit switches amongst warfarin products and brand and monitor
anti-coagulation after making changes.

Another patient, who reports a high level of drug
sensitivity, noticed that a particular generic of nortriptyline used for
chronic insomnia was more effective for him than others.

Thyroid medication is known to vary amongst the generics and
Synthroid brand in terms of clinical effects. While the FDA has deemed these
various products to be bioequivalent and interchangeable many endocrinologists
disagree. In attempt to address this
issue in 2004 a Joint Statement was issued by the major
endocrinology professional societies making recommendations on the topic.

The most recent
controversy regarding generics has to do with biological drugs, or
“biologics.” Because of the inherent complexity of these innovator drugs, which
are derived from living cells, the concept of “biosimilar” has replaced
bioequivalent for the generic products being developed.As reported last week in the New
York Times, the pharmaceutical industry is currently engaged intense
lobbying to prevent biosimilar generic biologics from coming to market as
competition to the numerous, ultra-expensive biologics whose patents will be
expiring in the near future.

The science behind the FDA approval process for generic drugs
is rigorous. My advice, it can be smart to try a generic. There is no evidence
that these products are of lower quality, or less effective than name brand
products—though they are not required to go through clinical efficacy trials.
However, be wary of minor fluctuations in the clinical effects of your medications
when switching between name brand and generic, and amongst different generics,
and be aware that your pharmacist may change your generic from one manufacturer
to another without your knowledge (the pill should look different).

What is your experience with generic medications versus name
brand products?

1 comment:

I am severely allergic to sulfa, lasix, HCTZ, shellfish, penicillin, iodine contrast dye. When I required hypertensive medication, it became a nightmare. Due to my asthma, beta blockers were impossible. Ace inhibitors give me a rash, including Lisinopril. Diovan works well and does not cause a reaction. My insurance company keeps insisting I can take Losartan instead, which would be much less expensive. We have tried four times, and each time I have a severe allergic response. The last time I had to use the Epi-Pen and go to the ER. I don't know what the difference is, but there is a difference. The pharmacy keeps insisting it is the same drug. I am proof it is NOT.

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I am a general internist, otherwise known as a primary care physician for adults. I grew up in Ann Arbor, Michigan, attended medical school at the
University of Michigan, and completed my residency training in internal
medicine at the University of Washington in Seattle. After my training I spent 12 years in practice at Emory University in Atlanta, where I served as clinician and teacher of medical residents. In my role as Director of Clinical Outcome Improvement at The Emory Clinic in General Medicine I developed expertise in the field of quality improvement. In particular, I led work to improve care for patients with chronic illness. This work fostered my interest in innovative models of primary care
delivery. In 2010 I founded Personalized Primary Care Atlanta, where I
currently practice.

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